Incidence of hepatocellular carcinoma in southeast iran.

BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is a well-known consequence of chronic liver disease (CLD). The aim of this study was to extract the HCC incidence rate in the province of Kerman, located in southern part of Iran, and compare the data with other parts of the country.


MATERIALS AND METHODS
All medical records related to HCC were collected through hospitals or outpatient services in public or private centers. The records of all oncology, radiotherapy, and pathology centers in Kerman province were actively searched between 1999 and 2006. The annual incidence of HCC around the country was calculated, using the national cancer registry database provided by the Health Ministry of IR Iran from 2005 to 2006. Using Stata version 8, the crude and age-sex-standardized annual incidence rates were computed.


RESULTS
The crude annual incidence rates of HCC per 100,000 persons in Kerman and Iran were 0.522 (95% CI = 0.238- 0.88) and 0.199 (95% CI = 0.167-0.234), respectively. When adjusting for age and sex, the annual incidence rates of HCC in Kerman and Iran were 0.7 (95% CI = 0.4-1.1) and 0.2 (95% CI = 0.2-0.3) per 100,000 persons, respectively (P<0.01).The mean age of patients in Kerman was around 5.5 years younger than other parts of Iran (56.17 ± 18.32 years versus 61.68 ± 14.62 years; P=0.004).


CONCLUSIONS
In general, the incidence of HCC is not very high in Iran; however, the higher incidence of HCC in Kerman and also the lower age of onset mandates further research to detect HCC's risk factors in this part of country.


Introduction
H epatocellular carcinoma (HCC), a malignant tumor originating from hepatocytes, is the sixth-most prevalent cancer worldwide. Furthermore, due to its poor prognosis, it is also the fourth leading cause of death related to cancer (1) . Although HCC is not generally common, it is an intractable disease (2) . Therefore, we have to pay special attention to the risk factors of HCC in order to decrease its burden on society. There is a great variation in the incidence of HCC between and even within countries. These differences might be due to regional variations in exposure to HCC risk factors. The annual incidence of HCC has been estimated to be high in Africa (24/100,000) and eastern areas of Asia (35/100,000); whereas its incidence is low in North America, Western Europe, and the Middle East (3-4/100,000) (3) . Although Iran is located in a low-risk region with an annual incidence well under 5 per 100,000 (2) , we could not find specific information about its distribution within the country. Because the main known HCC risk factors vary around the country, it is reasonable to presume that its incidence also varies significantly.
Some of the potent risk factors of HCC are now well-documented and include chronic viral hepatitis, cirrhosis, alcohol abuse, and Aflatoxin exposure (4) . However, other risk factors, such as smoking, obesity, and diabetes, are also associated with increased risk of HCC (5,6) . We did not find any specific information about the epidemiology of HCC in the literature on the Iranian population. There are a few published papers about the epidemiology of HCC risk factors such as Hepatitis B (7,8) and Hepatitis C (9) and their geographic distributions, but the incidence and geographical pattern of HCC are not clearly defined. The Iranian government's Department for Fighting Cancer includes a cancer registry program, which published its first report in 1986. In 1999 the executive guidelines for cancer registry were revised and the second report was published; however, it is thought that the second report captured only 18% of new cases. The last report, which is based on data from 2005, is estimated to reflect around 80% of new cancer cases in the country (10) . Kerman is a very wide province in southeast Iran, with a population of approximately 2.6 million. Traditionally, the lifestyle of its inhabitants, such as their diet, might increase the risk of HCC. For instance, this province produces more than 60% of the country's pistachios, which used to be a main source of dietary aflatoxin exposure. In addition, viral hepatitis used to be more or less common in this province, but generally not greater than the national average (8,11) . There are also two reports about the prevalence of positive HBs antigen in pregnant women in the Kerman province, and their estimated prevalence seems to be the same as the national figure (12,13) . Based on the above explanation, we explored the data from the national cancer registry and also the province's population-based registry in order to generate an acceptable annual incidence risk of HCC in Kerman and compare this figure with the national incidence.

Materials and Methods
We searched all databanks of cancer cases extensively, including all pathology, oncology, and radiology centers and medical documents and death registries within the Kerman province between 1999 and 2006. In this search, we extracted the data of all patients with any type of liver cancers to maximize our sensitivity to the detection of HCC. In addition, we searched the national cancer registry databank to find any possible Kermanian cases recorded in the data of other provinces. We excluded duplicate records by using the full names of cases. In order to compare the incidence of HCC in Kerman with the incidence in other areas in the country, the national and provincial figures in a few selective provinces were extracted from the cancer registry database. We selected six provinces because they have the most complete data in their cancer registry databanks (Esfahan, Razavi Khorasan, Khoozestan, Golestan, Ardebil, West Azerbaijan, Tehran, Fars, and Guilan). Because we expect the cancer registry in these provinces to have maximum sensitivity, the estimated incidence in Kerman (data from different sources) is more comparable with the incidence in these selected provinces.
The data were computerized using CanReg Software (produced by Iran's Ministry of Health through its cancer registry program). The statistical analysis was performed using Stata (version 8). The total populations of provinces and their age and sex distributions were extracted from the data from the Iranian national census in 2006. The Standardized incidence of HCC was calculated at both the provincial and national levels using WHO's world standard population. The 95% confidence intervals of the incidences were computed using a Poisson distribution and were compared using a Poisson regression model.

Results
We found the records of 333 cases labeled as liver tumor in Kerman between 1999 and 2006; among them, only 95 cases had confirmed HCC diagnosis; others were mostly metastases of other cancers to the liver. Only two new HCC cases were added to our records from the national cancer registry databank; these two cases sought their treatments outside of the Kerman province. The crude annual incidence risk in Kerman was 0.522 (95% CI = 0.283-0.88) per 100,000. After adjusting for age and sex, the standardized risk was 0.7 (95% CI = 0.4-1.1) per 100,000. The standardized risk in males was 0.9 (0.3-1.5) and in females was 0.4 (0.0-0.8). During 2005-2006, 484 cases of liver tumors were recorded in the cancer registry database around the country. Among them, 279 records had a confirmed diagnosis of HCC. The crude annual incidence risk of HCC in Iran was 0.199 (95% CI = 0.167-0.234) per 100,000. After adjusting for age and sex, the standardized risk was 0.2 (95% CI = 0.2-0.3) per 100,000. The to the synergistic effect of aflatoxin and hepatitis in the development of HCC (18) . However, due to some issues, such as improvements in people's lifestyles, turning attention away from the preservation of high-quality pistachio, and clearer definitions "health programs" by the Health Ministry of Iran, people's exposure to aflatoxin have decreased considerably in recent decades.
Some portion of the lower HCC incidence rate in Iran as a whole than in Kerman could be due to the low accuracy of the national cancer registry compared to the sensitivity of our multiple sources of active case findings in Kerman. However, because the diagnosis of HCC is not difficult, particularly in the advanced stages, we do not expect that this explanation by itself can explain such a wide difference between the incidence rates in Iran and Kerman. We also compared our estimates with those in provinces with high-quality cancer registries (Table 1), which showed that the crude annual incidence rate of HCC in Kerman was the highest of all provinces. In addition, in order to minimize this error, we only used the data from the last 2 years to estimate the national incidence rate. In general, we expect that the quality of the national cancer registry has been improved in recent years. In conclusion, we believe that the incidence of HCC in Kerman is greater than the rate in the whole country, although the rate is still very low compared to the global figure.